Low-dose ethanol ameliorates amnesia induced by a brief seizure model: the role of NMDA signaling

Objective: The present study aimed to evaluate the ameliorative effect of low-dose ethanol (Eth) on amnesia induced by a brief seizure model and the role of N-methyl D-aspartate (NMDA) signaling in this event. Materials and Methods: Four groups of rats (total number = 36; n = 9, each group) were used: control, Eth (0.5 g/kg/i.p.), pentylenetetrazole (PTZ) (60 mg/kg/i.p.), and Eth+PTZ. Eth was administered for 6 days before the single injection of PTZ, at minute dose that cannot induce memory impairment. The consequences of Eth pretreatment, coadministered with PTZ, were studied in an inhibitory avoidance (IA) memory model. The PTZ was injected 30 min prior to the IA memory test. Thereafter, locomotion, liver enzymes, and the Real-time PCR for NR1 subunit of NMDA receptor were studied. The statistical analyses were performed using the parametric/nonparametric ANOVA and the post-hoc tests. Results: Our findings revealed that Eth pretreatment significantly improved the IA memory impairment induced by PTZ (P < 0.001), and indicated no change in locomotion and serum ALT, but significantly differed for AST between the PTZ and PTZ groups (P = < 0.05). The Real-time PCR results indicate the decreased NR1 mRNA expression in Eth and PTZ groups and the increased NR1 mRNA expression in Eth+PTZ group, compared to the control group (P < 0.001); however, the NR1 mRNA expression was increased in the Eth+PTZ group, compared to PTZ group (P < 0.001). Conclusion: The present study provides evidence that the low-dose Eth can improve the amnesia induced by a brief seizure model presumably via NMDA signaling in a rat. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Adapted MMSE and TYM cognitive tests: how much powerful in screening for Alzheimer�s disease in Iranian people

Alzheimer�s disease (AD) is a major global health priority and providing an efficient way for early diagnosis of people developing dementia is important. The Mini-Mental State Examination (MMSE, total score = 30) and Test Your Memory (TYM, total score = 50) are widely used as screening tests for cognitive function. In the present study 174 subjects including healthy people (CON group) and those having Alzheimer�s disease (AD group) were introduced to MMSE and TYM cognitive tests adjusted to Iranian population. Sensitivities and specificities with optimal cut-off scores, area under curve (AUC), positive predictive value (PPV) and negative predictive value (NPV) were measured for both tests. The MMSE scores of the CON and AD groups were 23.77 ± 0.327 and 10.88 ± 0.762, respectively. The TYM scores were 44.32 ± 0.389 and 14.37 ± 1.368 in the CON and AD participants, respectively. Findings in the MMSE test were: AUC = 0.962, optimal cut-off score = 18.5, sensitivity = 0.90 and specificity = 0.96. Values in the TYM test were: AUC = 0.991, optimal cut-off score = 31, sensitivity = 0.90 and specificity = 1. We found no correlation between the cognitive performance and age in the CON group but a positive correlation in the AD patients. On the other hand, t-test analysis indicated that achievement of the test scores are significantly sex dependent, with more scores attained by the females. Taken together, in regard to correct classification rate (CCR); the TYM test seems to be more appropriate for cognitive screening in our study. However, considering an analogous AUC, both tests are comparable and have high sensitivity and specificity for discriminating between people with and without AD. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling

Epilepsy is one of the most common neurological disorders that severely affect life quality of many people worldwide. Ion transport in the neuronal membrane, inhibitory�excitatory mechanisms, and regulatory modulator systems have been implicated in the pathogenesis of epilepsy. A bidirectional communication is proposed between brain and gut where the brain modulates the gastrointestinal tract, and the gut can affect brain function and behavior. The gut microbiome takes an important role in health and disease where dysbiosis is involved in several neurological disorders. Probiotics as living microorganisms are beneficial to humans and animals when adequately administered. In the present work, we evaluated the effect of a probiotic bacteria mixture on seizure activity, cognitive function, and gamma-aminobutyric acid (GABA), nitric oxide (NO), malondealdehyde (MDA), and total antioxidant capacity (TAC) level of the brain tissue in the pentylenetetrazole (PTZ)-induced kindled rats. The Racine score and performance in water maze were considered as indices of the epileptic severity and the spatial learning and memory, respectively. We found that the probiotic supplementation substantially reduces seizure severity so that almost no probiotic-treated animals showed full kindling. The oral bacteriotherapy partially improved the spatial learning and memory in the kindled rats. The intervention decreased NO and MDA and increased TAC concentration of the brain. The probiotic treatment also increased the inhibitory neurotransmitter GABA. Our findings are the first preclinical report to show positive effect of probiotic bacteria on seizure-induced neurological disorders. Further investigation is required to answer the questions raised about the probable mechanisms involved. © 2019 Elsevier Inc

Does severity of Alzheimer's disease contribute to its responsiveness to modifying gut microbiota? A double blind clinical trial

Alzheimer's disease (AD) is associated with cognitive dysfunction. Evidence indicates that gut microbiota is altered in the AD and, hence, modifying the gut flora may affect the disease. In the previous clinical research we evaluated the effect of a probiotic combination on the cognitive abilities of AD patients. Since, in addition to pathological disorders, the AD is associated with changes in oxidant/antioxidant and inflammatory/anti-inflammatory biomarkers, the present work was designed to evaluate responsiveness of the inflammatory and oxidative biomarkers to the probiotic treatment. The control (CON) and probiotic (PRO) AD patients were treated for 12 weeks by the placebo and probiotic supplementation, respectively. The patients were cognitively assessed by Test Your Memory (TYM = 50 scores). Also serum concentrations of nitric oxide (NO), glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2' -deoxyguanosine (8-OHdG) and cytokines (TNF-α, IL-6, and IL-10) were measured. The cognitive test and the serum biomarkers were assessed pre- and post-treatment. According to TYM test 83.5 of the patients showed severe AD. The CON (12.86 ± 8.33) and PRO (-9.35 ± 16.83) groups not differently scored the cognitive test. Not pronounced change percent was found in the serum level of TNF-α (1.67 ± 1.33 vs. -0.15 ± 0.27), IL-6 (0.35 ± 0.17 vs. 2.18 ± 0.15), IL-10 (0.05 ± 0.10 vs. -0.70 ± 0.73), TAC (0.07 ± 0.07 and -0.06 ± 0.03), GSH (0.08 ± 0.05 and 0.04 ± 0.03) NO (0.11 ± 0.06 and 0.05 ± 0.09), MDA (-0.11 ± 0.03 and -0.17 ± 0.03), 8-OHdG (43.25 ± 3.01 and 42.70 ± 3.27) in the CON and PRO groups, respectively. We concluded that the cognitive and biochemical indications in the patients with severe AD are insensitive to the probiotic supplementation. Therefore, in addition to formulation and dosage of probiotic bacteria, severity of disease and time of administration deeply affects results of treatment. © 2018 Agahi, Hamidi, Daneshvar, Hamdieh, Soheili, Alinaghipour, Esmaeili Taba and Salami